The AIDS Clinical Trials Group (ACTG) has been at the forefront of clinical research to advance HIV therapeutics and improve the health of patients living with HIV/AIDS for 25 years. Rigorous scientific research conducted by the ACTG has laid the cornerstones for current HIV treatment guidelines. In this application for the competitive renewal of the ACTG we propose a transformative research agenda that draws on an international consortium of leading clinical and laboratory HIV Investigators in collaboration with a world-class Statistics and Data Management Center to design and conduct innovative interventional clinical trials that will significantly reduce the global burden of disease due to HV, TB and hepatitis. A newly restructured Leadership and Operations Center (LOC) is proposed to provide scientific leadership and fiscal and organizational management of the ACTG. The ACTG Executive Committee (AEC) will serve as the overarching governing body of the network. Transformative Science Groups will oversee the development and execution of the ACTG research agenda, which will be coordinated and prioritized by the Scientific Agenda Steering Committee (SASC). Protocol development, implementation, training and network evaluation will be facilitated by the Network Coordinating Center at Social & Scientific Systems, Inc. The LOC financial management group at Brigham and Women's Hospital (BWH) will oversee resource management and protocol fund distribution at the direction of the AEC. The LOC will assure the engagement of Community in all aspects of the ACTG, and will coordinate communication between all three components of the network. Specific aims of this proposal include: 1) to identify strategies to cure and/or achieve a functional cure for HIV; 2) to improve the diagnosis and treatment of tuberculosis, especially in those co-infected with HIV; 3) to identify strategies o cure Infectious hepatitis; 4) to prevent or improve the treatment of, non-infectious co-morbidities and evaluate novel Interventions targeting HIV Infection; 5) to Investigate and improve oral health outcomes in persons with HIV/AIDS ; and 6) to improve the treatment for viral related malignancies In HIV-infected adults. RELEVANCE: The studies proposed in this application will have a direct beneficial effect on the health of millions of people worldwide who are infected with or at risk for HIV, tuberculosis and viral hepatitis, transforming the health of patients with these infections. The clinical research conducted by the ACTG will lead to significantly reducing morbidity and mortality, particularly among populations disproportionately affected by HIV/AIDS